We wish to develop methods by which genes can be transferred from one mammalian cell to another by a virus-like particle. The approach will emphasize the use of pseudovirions for the delivery of a useful gene or the repair of a missing or defective gene. Pseudovirions, in this case, are defined as fragments of mammalian DNA (about 3 x 10 to the 6th power daltons in size) encapsulated by polyoma virus coats. In order to do this, we plan (a) to study the mechanisms by which polyoma pseudovirions are synthesized and what controls this synthesis; (b) to prepare polyoma pseudovirions containing human DNA and use these particles to attempt transduction and integrations in human cell cultures; (c) to use mouse pseudovirions for transduction experiments in the whole mouse as well as cultured mouse cells; (d) to produce virus particles containing specific genes by the in vitro assembly of polyoma coat proteins and DNA. We plan to study the fate of such transferred mammalian genes; for example, are they degraded, integrated in the recipient cell chromosomes and/or phenotypically expressed? Although we are primarily interested in understanding the basic molecular aspects of the transfer and integration of genetic information in mammalian cells, we believe the results of this work will be important eventually in developing a gene delivery system to facilitate the use of DNA as a therapeutic agent for the treatment of mammalian inherited metabolic diseases.